Hemophilia is a group of recessive sex-linked X-chromosome hereditary genetic disorders that impair the body's ability to control coagulation. Hemophilia A, a clotting factor VIII deficiency, is the most common form, occurring at about 1 in 5,000-10,000 male births. Hemophilia B, a clotting factor IX deficiency, is less common and occurs at about 1 in about 20,000-34,000 male births. Hemophilia C is an autosomal genetic disorder (not X-linked) involving a lack of functional clotting Factor XI. Unlike Hemophilia A and B, Hemophilia C is not completely recessive and heterozygous individuals also show increased bleeding times. However, it predominantly occurs in Jews of Ashkenazi descent. It is the fourth most common coagulation disorder after von Willebrand disease and Hemophilia A and B. von Willebrand disease is the most common hereditary coagulation abnormality in humans, although it can also be acquired as a result of other medical conditions. It arises from a deficiency of von Willebrand factor, a protein that is required for platelet adhesion. Generally, patients having Hemophilia C or von Willebrand disease do not require treatment, although they are at increased risk for bleeding.
Hemophilia results in lowered plasma levels of the coagulation factors needed for normal clotting. Therefore, when a blood vessel is injured, the missing coagulation factors prevent fibrin formation, which is necessary to maintain a blood clot. Thus a hemophiliac does not bleed more intensely than a normal person, but rather bleeds for a much longer amount of time. In severe hemophiliacs even a minor injury can result in blood loss lasting days, weeks, or longer. If the bleeding occurs in areas such as the brain it can be fatal.
Although there is no cure for hemophilia, it can be controlled with regular infusions of the deficient clotting factor, i.e. factor VIII in Hemophilia A or factor IX in Hemophilia B. The clotting factor used for replacement can be either isolated from human blood serum, made recombinantly, or a combination of the two. Some hemophiliacs develop an immune response to the clotting factors given to them, so the amount of clotting factor has to be increased or non-human replacement factors must be given, such as porcine factor VIII. Although expensive, recombinant clotting factor products offer higher purity and safety than those derived from human serum or non-human sources. It is, therefore, desirable to have a safe, human source for delivery or production of clotting factors, preferably one that does not need to be continually or repeatedly administered. It is an object of the subject invention to provide such a therapeutic option for treating hemophilia.